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1.
Sci Rep ; 11(1): 8692, 2021 04 22.
Article in English | MEDLINE | ID: covidwho-1199310

ABSTRACT

A metal nanoparticle composite, namely TPNT1, which contains Au-NP (1 ppm), Ag-NP (5 ppm), ZnO-NP (60 ppm) and ClO2 (42.5 ppm) in aqueous solution was prepared and characterized by spectroscopy, transmission electron microscopy, dynamic light scattering analysis and potentiometric titration. Based on the in vitro cell-based assay, TPNT1 inhibited six major clades of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with effective concentration within the range to be used as food additives. TPNT1 was shown to block viral entry by inhibiting the binding of SARS-CoV-2 spike proteins to the angiotensin-converting enzyme 2 (ACE2) receptor and to interfere with the syncytium formation. In addition, TPNT1 also effectively reduced the cytopathic effects induced by human (H1N1) and avian (H5N1) influenza viruses, including the wild-type and oseltamivir-resistant virus isolates. Together with previously demonstrated efficacy as antimicrobials, TPNT1 can block viral entry and inhibit or prevent viral infection to provide prophylactic effects against both SARS-CoV-2 and opportunistic infections.


Subject(s)
Gold/pharmacology , Influenza A Virus, H1N1 Subtype/physiology , Influenza A Virus, H5N1 Subtype/physiology , SARS-CoV-2/physiology , Silver/pharmacology , Zinc Oxide/pharmacology , Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Drug Resistance, Viral/drug effects , Food Additives/pharmacology , Gold/chemistry , HEK293 Cells , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H5N1 Subtype/drug effects , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Oseltamivir/pharmacology , Particle Size , Protein Binding/drug effects , SARS-CoV-2/drug effects , Silver/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects , Zinc Oxide/chemistry
2.
Int J Nanomedicine ; 16: 2689-2702, 2021.
Article in English | MEDLINE | ID: covidwho-1186650

ABSTRACT

Background: The COVID-19 pandemic is requesting highly effective protective personnel equipment, mainly for healthcare professionals. However, the current demand has exceeded the supply chain and, consequently, shortage of essential medical materials, such as surgical masks. Due to these alarming limitations, it is crucial to develop effective means of disinfection, reusing, and thereby applying antimicrobial shielding protection to the clinical supplies. Purpose: Therefore, in this work, we developed a novel, economical, and straightforward approach to promote antimicrobial activity to surgical masks by impregnating silver nanoparticles (AgNPs). Methods: Our strategy consisted of fabricating a new alcohol disinfectant formulation combining special surfactants and AgNPs, which is demonstrated to be extensively effective against a broad number of microbial surrogates of SARS-CoV-2. Results: The present nano-formula reported a superior microbial reduction of 99.999% against a wide number of microorganisms. Furthermore, the enveloped H5N1 virus was wholly inactivated after 15 min of disinfection. Far more attractive, the current method for reusing surgical masks did not show outcomes of detrimental amendments, suggesting that the protocol does not alter the filtration effectiveness. Conclusion: The nano-disinfectant provides a valuable strategy for effective decontamination, reuse, and even antimicrobial promotion to surgical masks for frontline clinical personnel.


Subject(s)
Anti-Infective Agents/pharmacology , Disinfectants/pharmacology , Masks , Metal Nanoparticles/chemistry , Silver/pharmacology , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/prevention & control , COVID-19/transmission , Chick Embryo , Disinfectants/administration & dosage , Disinfectants/chemistry , Disinfection/methods , Dynamic Light Scattering , Equipment Reuse , Humans , Influenza A Virus, H5N1 Subtype/drug effects , Masks/virology , Metal Nanoparticles/administration & dosage , Microbial Sensitivity Tests , Silver/chemistry , Spectroscopy, Fourier Transform Infrared , Textiles , X-Ray Diffraction
3.
Front Immunol ; 11: 598444, 2020.
Article in English | MEDLINE | ID: covidwho-1013338

ABSTRACT

Patients infected with SARS-CoV-2 show a wide spectrum of clinical manifestations ranging from mild febrile illness and cough up to acute respiratory distress syndrome, multiple organ failure, and death. Data from patients with severe clinical manifestations compared to patients with mild symptoms indicate that highly dysregulated exuberant inflammatory responses correlate with severity of disease and lethality. Epithelial-immune cell interactions and elevated cytokine and chemokine levels, i.e. cytokine storm, seem to play a central role in severity and lethality in COVID-19. The present perspective places a central cellular pro-inflammatory signal pathway, NF-κB, in the context of recently published data for COVID-19 and provides a hypothesis for a therapeutic approach aiming at the simultaneous inhibition of whole cascades of pro-inflammatory cytokines and chemokines. The simultaneous inhibition of multiple cytokines/chemokines is expected to have much higher therapeutic potential as compared to single target approaches to prevent cascade (i.e. redundant, triggering, amplifying, and synergistic) effects of multiple induced cytokines and chemokines in critical stage COVID-19 patients.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , NF-kappa B/antagonists & inhibitors , Proteasome Inhibitors/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/pathology , Cytokines/blood , Disease Models, Animal , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H5N1 Subtype/drug effects , Mice , Mice, Inbred BALB C , Orthomyxoviridae Infections/drug therapy , SARS-CoV-2/immunology
4.
Antiviral Res ; 181: 104885, 2020 09.
Article in English | MEDLINE | ID: covidwho-663032

ABSTRACT

Influenza A virus (IAV) infection represents a global health challenge. Excavating antiviral active components from traditional Chinese medicine (TCM) is a promising anti-IAV strategy. Our previous studies have demonstrated that 14-deoxy-11,12-didehydroandrographolide (DAP), a major ingredient of a TCM herb called Andrographis paniculata, shows anti-IAV activity that is mainly effective against A/chicken/Hubei/327/2004 (H5N1), A/duck/Hubei/XN/2007 (H5N1), and A/PR/8/34 (H1N1) in vitro and in vivo. However, the underlying anti-IAV molecular mechanism of DAP needs further investigation. In the present work, we found that DAP can significantly inhibit the apoptosis of human lung epithelial (A549) cells infected with A/chicken/Hubei/327/2004 (H5N1). After DAP treatment, the protein expression levels of cleaved PARP, cleaved caspase-3, and cleaved caspase-9, and the activities of caspase-3 and caspase-9 in H5N1-infected A549 cells were all obviously downregulated. However, DAP had no inhibitory effect on caspase-8 activity and cleaved caspase-8 production. Meanwhile, the efficacy of DAP in reducing the apoptotic cells was lost after using the inhibitor of caspase-3 or caspase-9 but remained intact after the caspase-8 inhibitor treatment. Moreover, DAP efficiently attenuated the dissipation of mitochondrial membrane potential, suppressed cytochrome c release from the mitochondria to the cytosol, and decreased the protein expression ratio of Bax/Bcl-2 in the mitochondrial fraction. Furthermore, the silencing of caspase-9 reduced the yield of nucleoprotein (NP) and disabled the inhibitory ability of DAP in NP production in A549 cells. Overall results suggest that DAP exerts its antiviral effects by inhibiting H5N1-induced apoptosis on the caspase-9-dependent intrinsic/mitochondrial pathway, which may be one of the anti-H5N1 mechanisms of DAP.


Subject(s)
Antiviral Agents/pharmacology , Apoptosis/drug effects , Caspase 9/genetics , Diterpenes/pharmacology , Influenza A Virus, H5N1 Subtype/drug effects , Signal Transduction/drug effects , A549 Cells , Animals , Caspase 9/metabolism , Cell Survival/drug effects , Dogs , Drug Discovery , Humans , Madin Darby Canine Kidney Cells
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